Cough desensitization treatment: A randomized, sham-controlled pilot trial for patients with refractory chronic cough

Slovarp, Laurie; Reynolds, Jane; Dailey, Bozarth; Popp, Sarah; Campbell, Sarah; Morkrid, Paige

doi:10.1016/j.rmed.2022.106739

Cited by 8 publications

(8 citation statements)

References 51 publications

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“…This would explain why exercise may still trigger a short-term cough right after exercise but decreases the tendency to have prolonged cough. Moreover, capsaicin, another hypertussive irritant in addition to cold air, triggers cough after a single exposure but has been suggested to decrease cough sensitivity and to treat chronic cough as repeated dosing 28 29. This similarity between capsaicin and repeated exposure to cold air further supports the idea that different mechanisms are involved in cough after exercise and prolonged cough.…”

Section: Discussionmentioning

confidence: 91%

Cross-country skiers often experience respiratory symptoms during and after exercise but have a low prevalence of prolonged cough

Mäki-Heikkilä

Koskela

Karjalainen

et al. 2023

BMJ Open Sport Exerc Med

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BackgroundCross-country skiers train and compete during the winter for long periods of time in subfreezing conditions, which strains the airways and provokes respiratory symptoms. This study aimed to compare the prevalence of exercise-related symptoms and prolonged cough in competitive cross-country skiers versus the general population and to investigate the association between these symptoms and asthma.MethodsA questionnaire was sent to Finnish cross-country skiers (n=1282) and a random sample of the general population (n=1754), with response rates of 26.9% and 19.0%, respectively.ResultsBoth groups were mostly asymptomatic at rest, but symptoms were increased in both groups during and after exercise. Cough was more prevalent after exercise in skiers and phlegm production was more common during and after exercise in skiers. Asthma did not provoke specific symptoms, but symptom prevalence was higher in asthmatic individuals. Skiers had a higher prevalence of cough after exercise (60.6% vs 22.8%, p<0.001) compared with controls, but controls had a higher prevalence of prolonged cough (4.1% vs 9.6%, p=0.004). In participants without asthma, cold air triggered symptoms more often in skiers than controls, while strong odours triggered symptoms more often in asthmatic controls than skiers. Chronic cough lasting more than 8 weeks was rare, reported by 4.8% of controls and 2.0% of skiers.ConclusionCross-country skiers, especially those with asthma, experience a higher burden of exercise-related respiratory symptoms compared with controls. However, repeated exposure to cold air does not appear to result in long-term hypersensitivity of the cough reflex arc.

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Section: Discussionmentioning

confidence: 91%

Cross-country skiers often experience respiratory symptoms during and after exercise but have a low prevalence of prolonged cough

Mäki-Heikkilä

Koskela

Karjalainen

et al. 2023

BMJ Open Sport Exerc Med

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“…In particular, conducting informal assessments using airway and cough challenges is advantageous when preparation and administration are clinically practical ( Vertigan & Gibson, 2016 ). In addition, increasingly innovative approaches with tussigenic agents are being implemented in nonpharmacological treatments for cough disorders ( Borders et al, 2022 ; Hegland, Davenport, et al, 2016 ; Slovarp et al, 2022 ). Expanding research methods in airborne irritants and tussive stimuli may further elucidate the mediating factors and mechanisms underlying normal and pathological cough.…”

Section: Discussionmentioning

confidence: 99%

“…Although it has been postulated that quantifying chemical stimuli is problematic for inhalation challenges ( Vertigan & Gibson, 2016 ), research methods in the chemosensory sciences actually provide relevant directions to assist with standardizing chemical stimuli for clinical assessment procedures ( Novaleski et al, 2021 ). Moreover, tussigenic agents such as capsaicin have therapeutic applications across the continuum of disordered cough, specifically with nonpharmacological interventions in the form of behavioral speech therapy ( Borders et al, 2022 ; Hegland, Davenport, et al, 2016 ; Slovarp et al, 2022 ). The ability to easily use nonaerosolized stimuli outside clinical settings may enhance therapeutic benefits and patient adherence, as demonstrated with exposures to odorant stimuli during olfactory training for postviral olfactory dysfunction ( Altundag et al, 2015 ; Saatci et al, 2020 ; Yuan et al, 2021 ).…”

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confidence: 99%

Characterization of Ethyl Butyrate–Induced Cough Before and After Breath Control Techniques in Healthy Adults

Novaleski

Wheeler-Hegland

Aleksandruk

et al. 2023

Am J Speech Lang Pathol

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Purpose: Methods for cough elicitation frequently involve aerosolized tussive agents. Here, we sought to determine whether healthy individuals demonstrate a quantifiable cough response after inhaling a volatile ester and if breath control techniques modify this chemically induced cough response. Method: Sixty adult male and female participants inhaled prepared liquid dilutions of ethyl butyrate dissolved in paraffin oil at 20%, 40%, and 60% v/v concentrations in triplicate, with presentation order randomized. We delivered stimuli through a face mask connected to an olfactometer and respiratory pneumotachograph. Participants rated sensations of their urge to cough and pleasantness of the odor while cough airflow was measured. Following baseline testing, participants were randomized to implement pursed-lip breathing or slow-paced breathing after inhaling ethyl butyrate to determine the effects of breath control on cough measures. Results: Inhaled ethyl butyrate elicited cough in 70% of participants. Higher concentrations of ethyl butyrate resulted in significantly greater sensation of the urge to cough, F (2, 80) = 10.72, p < .001, and significantly more generated coughs, F (2, 63) = 13.14, p < .001. Compared to baseline, participants rated significantly decreased urge to cough during breath control techniques, F (1, 40) = 11.01, p = .0019. No significant changes were observed in the number of generated coughs between baseline and breath control techniques, F (1, 31) = 7.23, p = .01. Conclusions: Airborne ethyl butyrate is a tussigenic agent in humans. Our findings provide opportunities for future research directions in normal and disordered cough responses to volatile compounds.

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“…For these reasons, we previously developed and showed preliminary evidence for a treatment approach called cough desensitization treatment (CDT), where UTC is elicited in a controlled manner in a therapeutic context to facilitate successful cough suppression. In CDT pilot 1, patients with CHS, who previously had not responded to BCST, were exposed to progressive doses of inhaled aerosolized capsaicin via a nebulizer and coached to suppress cough (42). Following six sessions of CDT, 6/8 (75%) participants experienced a clinically meaningful improvement in cough-related quality of life as measured by the Leicester Cough Questionnaire (LCQ) (43).…”

Section: Introductionmentioning

confidence: 99%

Cough Desensitization Treatment for Patients with Refractory Chronic Cough: Results of a Second Pilot Randomized Control Trial

Slovarp

Reynolds

Tolbert

et al. 2023

Preprint

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Objective The purpose of this study was to collect pilot efficacy data on a novel treatment for refractory chronic cough (RCC), which we call cough desensitization treatment (CDT). Design and Methods In this parallel cohort, sham-controlled, randomized controlled trial, 21 adults with RCC were randomly assigned to 12 sessions of either CDT (progressive doses of aerosolized capsaicin while behaviorally suppressing cough; n = 11) or a sham treatment (repeated exposure to aerosolized saline; n = 9). The Leicester Cough Questionnaire (LCQ) was the primary outcome measure. Perceived cough severity with a visual analogue scale and cough challenge testing (for measuring cough-reflex sensitivity) were secondary outcome measures. Data were analyzed with mixed effects linear regression and follow-up contrasts. Results Results on all measures favored CDT. Excluding one sham participant, whose baseline LCQ scores were deemed unreliable, mean change in LCQ at 3-weeks post treatment was 6.35 and 2.17 in the CDT and sham groups, respectively. There was moderate to strong evidence of a greater improvement in the CDT group in total LCQ score (p = .058) and LCQ Psychological domain (p = .026) and Physical domain (p = .045) scores. Strong evidence was found for a greater reduction in urge-to-cough during CCT in the CDT group (p = .037) and marginal for a reduction in the capsaicin cough-reflex sensitivity (p = .094). There was weak evidence of a greater reduction in cough severity in the CDT group (p = .103). Discussion Although the study is limited due to the small sample size, the data provide additional evidence supporting further research on CDT. CDT resulted in a greater change in the primary efficacy measure (LCQ) than both pharmaceutical and behavioral treatments currently found in the literature. Trial Registration This trial (NCT05226299) was registered on Clinicaltrials.gov on 07/02/2022.

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Cough desensitization treatment: A randomized, sham-controlled pilot trial for patients with refractory chronic cough

Cited by 8 publications

References 51 publications

Cross-country skiers often experience respiratory symptoms during and after exercise but have a low prevalence of prolonged cough

Cross-country skiers often experience respiratory symptoms during and after exercise but have a low prevalence of prolonged cough

Characterization of Ethyl Butyrate–Induced Cough Before and After Breath Control Techniques in Healthy Adults

Cough Desensitization Treatment for Patients with Refractory Chronic Cough: Results of a Second Pilot Randomized Control Trial

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